The main objective of this study is the investigation of the possible uses of carbohydrate moieties or carbohydrate analogs in mediating a selective therapeutic effect against tumor cells. Conjugation of active antiproliferative agents with simple sugars may result in agents that manifest less nonspecific toxicity due to increased selective uptake or activitation by tumor cells. It is known that liver can rapidly clear desialted glycoproteins from the circulation and that cell surface receptors showing specificity for terminal galactosyl residues are responsible for initiating this phenomenon. The cell surface receptors may be enzymatic in nature and the presence of certain cell surface glycosyltransferases on L1210 leukemic cells have been documented in this laboratory by use of electron microscopic autoradiography. Further biochemical characterization of the ectoenzyme system and the resultant labeled cell surface sialoglycoproteins will be performed utilizing slab SDS-polyacrylamide gel electrophoresis. These cell surface ectoglycosyltransferases may bind carbohydrate-drug complexes thereby initiating a specific selective drug uptake process. Colchicine-sugar analogs containing various different hexoses will be incubated with several types in tissue culture. The drug concentration necessary for growth inhibition for those drug-sugar complexes will be determined. Perhaps the addition of a specific sugar to the parent compound will affect its action on a particular tumor cell type. This may come about by specific drug uptake mediated enzymatically or by specific drug activation mediated by high levels of intracellular glycosidase levels. Therefore cellular glycosidase activities will also be monitored in the cell types used in these studies. Finally, carbohydrate analogs bearing various substituent groups have been synthesized and will be tested in tissue culture to determine whether these agents can inhibit or modify the synthesis of cell glycoconjugates. BIBLIOGRAPHIC REFERENCES: Bernacki, R.J. and Gurtoo, H.L. (1975). Differential inhibition of rat liver sialyltransferase(s) by various aflatoxins and their metabolites. Res. Commun. Chem. Pathol. Pharmacol. 10, 681-692. Porter, C.W. and Bernacki, R.J. (1975). Ultrastructural evidence for ectosialyltransferase systems. Nature 256, 648-650.